RESUMEN
Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) has been suspected of causing de novo copy number variation. To explore this issue, here we perform a whole-genome and transcriptome analysis of 20 human iPSC lines derived from the primary skin fibroblasts of seven individuals using next-generation sequencing. We find that, on average, an iPSC line manifests two copy number variants (CNVs) not apparent in the fibroblasts from which the iPSC was derived. Using PCR and digital droplet PCR, we show that at least 50% of those CNVs are present as low-frequency somatic genomic variants in parental fibroblasts (that is, the fibroblasts from which each corresponding human iPSC line is derived), and are manifested in iPSC lines owing to their clonal origin. Hence, reprogramming does not necessarily lead to de novo CNVs in iPSCs, because most of the line-manifested CNVs reflect somatic mosaicism in the human skin. Moreover, our findings demonstrate that clonal expansion, and iPSC lines in particular, can be used as a discovery tool to reliably detect low-frequency CNVs in the tissue of origin. Overall, we estimate that approximately 30% of the fibroblast cells have somatic CNVs in their genomes, suggesting widespread somatic mosaicism in the human body. Our study paves the way to understanding the fundamental question of the extent to which cells of the human body normally acquire structural alterations in their DNA post-zygotically.
Asunto(s)
Variaciones en el Número de Copia de ADN/genética , Células Madre Pluripotentes Inducidas/metabolismo , Mosaicismo , Piel/metabolismo , Diferenciación Celular , Células Cultivadas , Reprogramación Celular , Células Clonales , Fibroblastos/citología , Perfilación de la Expresión Génica , Genoma Humano/genética , Humanos , Células Madre Pluripotentes Inducidas/citología , Masculino , Neuronas/citología , Reacción en Cadena de la Polimerasa , Reproducibilidad de los Resultados , Piel/citologíaRESUMEN
BACKGROUND: Women are at a greater risk for knee osteoarthritis (OA), but reasons for this greater risk in women are not well understood. It may be possible that differences in cartilage composition and walking mechanics are related to greater OA risk in women. QUESTIONS/PURPOSES: (1) Do women have higher knee cartilage and meniscus T1ρ than men in young healthy, middle-aged non-OA and OA populations? (2) Do women exhibit greater static and dynamic (during walking) knee loading than men in young healthy, middle-aged non-OA and OA populations? METHODS: Data were collected from three cohorts: (1) young active (<35 years) (20 men, 13 women); (2) middle-aged (≥35 years) without OA (Kellgren-Lawrence [KL] grade < 2) (43 men, 65 women); and (3) middle-aged with OA (KL>1) (18 men, 25 women). T1ρ and T2 relaxation times for cartilage in the medial knee, lateral knee, and patellofemoral compartments and medial and lateral menisci were quantified with 3.0-T MRI. A subset of the participants underwent three-dimensional motion capture during walking for calculation of peak knee flexion and adduction moments, flexion and adduction impulses, and peak adduction angle. Differences in MR, radiograph, and gait parameters between men and women were compared in the three groups separately using multivariate analysis of variance. RESULTS: Women had higher lateral articular cartilage T1ρ (men=40.5 [95% confidence interval {CI}, 38.8-42.3] ms; women=43.3 [95% CI, 41.9-44.7] ms; p=0.017) and patellofemoral T1ρ (men=44.4 [95% CI, 42.6-46.3] ms; women=48.4 [95% CI, 46.9-50.0] ms; p=0.002) in the OA group; and higher lateral meniscus T1ρ in the young group (men=15.3 [95% CI, 14.7-16.0] ms; women=16.4 [95% CI, 15.6-17.2] ms; p=0.045). The peak adduction moment in the second half of stance was lower in women in the middle-aged (men=2.05 [95% CI, 1.76-2.34] %BW*Ht; women=1.66 [95% CI, 1.44-1.89] %BW*Ht; p=0.037) and OA (men=2.34 [95% CI, 1.76-2.91] %BW*Ht; women=1.42 [95% CI, 0.89-1.94] %BW*Ht; p=0.022) groups. Static varus from radiographs was lower in women in the middle-aged (men=178° [95% CI, 177°-179°]; women=180° [95% CI, 179°-181°]; p=0.002) and OA (men=176° [95% CI, 175°-178°]; women=180° [95% CI, 179°-181°]; p<0.001) groups. Women had lower varus during walking in all three groups (young: men=4° [95% CI, 3°-6°]; women=2° [95% CI, 0°-3°]; p=0.013; middle-aged: men=2° [95% CI, 1°-3°]; women=0° [95% CI, -1° to 1°]; p=0.015; OA: men=4° [95% CI, 2°-6°]; women=0° [95% CI, -2° to 2°]; p=0.011). Women had a higher knee flexion moment (men=4.24 [95% CI, 3.58-4.91] %BW*Ht; women 5.40 [95% CI, 4.58-6.21] %BW*Ht; p=0.032) in the young group. CONCLUSIONS: These data demonstrate differences in cartilage composition and gait mechanics between men and women in young healthy, middle-aged healthy, and OA cohorts. Considering the cross-sectional nature of the study, longitudinal research is needed to investigate if these differences in cartilage composition and walking mechanics are associated with a greater risk of lateral tibiofemoral or patellofemoral OA in women. Future studies should also investigate the relative risk of lateral versus medial patellofemoral cartilage degeneration risk in women compared with men. LEVEL OF EVIDENCE: Level III, retrospective study.
Asunto(s)
Cartílago Articular/patología , Articulación de la Rodilla/patología , Articulación de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/patología , Osteoartritis de la Rodilla/fisiopatología , Caminata , Adulto , Factores de Edad , Anciano , Fenómenos Biomecánicos , Cartílago Articular/diagnóstico por imagen , Distribución de Chi-Cuadrado , Estudios Transversales , Femenino , Marcha , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Análisis Multivariante , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/etiología , Radiografía , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Estrés Mecánico , Soporte de PesoRESUMEN
Arthroscopic knee surgery is a common trigger for lower extremity complex regional pain syndrome (CRPS). Few studies assess nerve block catheters for CRPS treatment; they do not appear to be studies of regional anesthesia to treat CRPS that occurs after knee surgery. We present a case of CRPS-I triggered by knee surgery on multiple prior occasions but finally prevented by perineural adductor canal catheter placement. The literature presents only moderate evidence supporting interventions such as intravenous regional anesthesia and sympathetic blockade; continuous nerve blockade may be an effective treatment of CRPS-I and in particular postoperative CRPS-I.
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Síndromes de Dolor Regional Complejo , Anestésicos Locales , Artroscopía , Catéteres , Síndromes de Dolor Regional Complejo/prevención & control , HumanosRESUMEN
OBJECTIVE: To identify factors associated with online patient ratings and comments for a nationwide sample of otolaryngologists. METHODS: Ratings, demographic information, and written comments were obtained for a random sample of otolaryngologists from HealthGrades.com and Vitals.com . Online Presence Score (OPS) was based on 10 criteria, including professional website and social media profiles. Regression analyses identified factors associated with increased rating. We evaluated for correlations between OPS and other attributes with star rating and used chi-square tests to evaluate content differences between positive and negative comments. RESULTS: On linear regression, increased OPS was associated with higher ratings on HealthGrades and Vitals; higher ratings were also associated with younger age on Vitals and less experience on HealthGrades. However, detailed correlation studies showed weak correlation between OPS and rating; age and graduation year also showed low correlation with ratings. Negative comments more likely focused on surgeon-independent factors or poor bedside manner. CONCLUSION: Though younger otolaryngologists with greater online presence tend to have higher ratings, weak correlations suggest that age and online presence have only a small impact on the content found on ratings websites. While most written comments are positive, deficiencies in bedside manner or other physician-independent factors tend to elicit negative comments.
Asunto(s)
Competencia Clínica , Atención a la Salud , Internet , Otorrinolaringólogos/normas , Satisfacción del Paciente , Cirujanos/normas , Adulto , Atención a la Salud/normas , Femenino , Humanos , Masculino , Estados Unidos , Recursos HumanosRESUMEN
OBJECTIVE: To describe sinus procedure trends from 2000 to 2014, particularly following the introduction of balloon sinuplasty Common Procedural Technology (CPT) codes in 2011. STUDY DESIGN: Retrospective review of Medicare billing data available to the public. METHODS: Procedure and beneficiary data from 2000 to 2014 and provider data from 2012 to 2014 were obtained online from the Centers for Medicare and Medicaid Services. Sinus CPT codes were classified as balloon sinus procedure (BSP) or nonballoon sinus procedure (nBSP). Providers billing for sinus procedures were categorized as BSP only, nBSP only, or both. For comparison, data on septoplasty procedures from 2000 to 2014 were obtained. RESULTS: From 2000 to 2014, the total number of sinus procedures per 10 thousand beneficiaries (PP10K) nationwide increased by 3.7% annually. From 2011 to 2014, nBSP PP10K decreased by 3.1% annually, and BSP PP10K increased by 59% annually. Septoplasty PP10K changed by < 1% annually between 2000 and 2014. States with the highest BSP PP10K from 2012 to 2014 were Kansas, Texas, and Louisiana. Providers performing sinus procedures increased by 30.9% from 2012 to 2014. There was a 244% increase in BSP-only providers, a 0.7% increase in nBSP-only providers, and an 83.3% increase in providers using both. Septoplasty providers increased by 4.1%. CONCLUSION: Although the total number of sinus procedures increased from 2000 to 2014, the number of BSP increased at a substantially greater rate since the introduction of CPT codes for these procedures in 2011. Nationwide increases in sinus providers were driven by new providers performing balloon-guided procedures. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1976-1982, 2017.
Asunto(s)
Medicare/estadística & datos numéricos , Senos Paranasales/cirugía , Anciano , Current Procedural Terminology , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de Tiempo , Estados UnidosRESUMEN
This study assessed the effects of static loading on MRI relaxation times of menisci in individuals with and without radiographic knee OA. High-resolution fast spin-echo (FSE) and T(1ρ)/T(2) relaxation time MR sequences were obtained with and without loading at 50% body weight in 124 subjects. T(1ρ)/T(2) relaxation times were calculated in menisci, and meniscus lesions were assessed through clinical grading. Student's t-test compared OA and control unloaded relaxation times as well as within-group changes with loading, Generalized Linear Models evaluated zonal variation, and ANCOVA compared loading response between groups. Unloaded T(1ρ) and T(2) in the middle and inner zones of the lateral anterior horn and outer zone of the medial posterior horn were significantly higher in OA and suggest that meniscal OA change occurs unevenly. Zonal T(1ρ) and T(2) showed differing patterns between anterior and posterior horns, suggesting differences in macromolecular organization. Significant increases with loading were seen largely in the T(2) of controls and less frequently in subjects with OA. In the medial posterior horn, T(1ρ) and T(2) decreased with loading in OA but changed negligibly in controls; these significantly different loading responses between groups may indicate load transmission failure in OA menisci.
Asunto(s)
Meniscos Tibiales/fisiopatología , Osteoartritis de la Rodilla/fisiopatología , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Meniscos Tibiales/patología , Persona de Mediana Edad , Osteoartritis de la Rodilla/patología , Soporte de PesoRESUMEN
STUDY DESIGN: Cross-sectional. OBJECTIVES: To investigate the association between knee loading- related osteoarthritis (OA) risk factors (obesity, malalignment, and physical activity) and medial knee laminar (superficial and deep) T1rho and T2 relaxation times. BACKGROUND: The interaction of various modifiable loading-related knee risk factors and cartilage health in knee OA is currently not well known. METHODS: Participants with and without knee OA (n = 151) underwent magnetic resonance imaging at 3 T for superficial and deep cartilage T1rho and T2 magnetic resonance relaxation times in the medial femur (MF) and medial tibia (MT). Other variables included radiographic Kellgren-Lawrence (KL) grade, alignment, pain and symptoms using the Knee injury and Osteoarthritis Outcome Score, and physical activity using the International Physical Activity Questionnaire (IPAQ). Individuals with a KL grade of 4 were excluded. Group differences were calculated using 1-way analysis of variance, adjusting for age and body mass index. Linear regression models were created with age, sex, body mass index, alignment, KL grade, and the IPAQ scores to predict the laminar T1rho and T2 times. RESULTS: Total IPAQ scores were the only significant predictors among the loading-related variables for superficial MF T1rho (P = .005), deep MT T1rho (P = .026), and superficial MF T2 (P = .049). Additionally, the KL grade predicted the superficial MF T1rho (P = .023) and deep MT T1rho (P = .022). CONCLUSION: Higher physical activity levels and worse radiographic severity of knee OA, but not obesity or alignment, were associated with worse cartilage composition.